Millions of workers, including over 500,000 welders employed in the United States, have been exposed to excessive metals. Human and animal studies have strongly linked metal exposure to neurophysiological disorders and neurodegenerative diseases. Manganese (Mn) is one of the most significant metal neuro- toxicants among workers. Many occupational studies have documented Mn toxicity. However, the threshold of Mn exposure, the mechanism of the toxicity of Mn, and the interaction of Mn with other metals (such as lead and mercury) are unknown and therefore deserve further investigation. One pending issue in assessment of Mn exposure pertains to the selection of proper biomarker. Over 40% of Mn in human body is stored in bone, which renders bone Mn to be the ideal biomarkers to assess cumulative Mn in the body with long-term, low dose exposure, a pattern typically seen among workers occupationally exposed to Mn. In this project, a novel neutron activation analysis technology will be developed to noninvasively quantify Mn in bone in vivo. Later we will apply this technology in a larger project to study the possible synergistic neurotoxic effect of the exposure of metal mixtures among worker populations. Our central hypothesis to be tested in this proposal is that a novel transportable neutron activation analysis technology can be developed and validated for non invasive in vivo quantification of Mn in bone. We will conduct a series of Monte Carlo simulations to select the best design of the system, set up the system based on the chosen design, optimize the design with experiments, and develop new algorithms to analyze the data and calibrate the system. At the completion of this project, a novel technology for cumulative Mn exposure assessment will be established. The new technology and knowledge will help to fill the data gaps regarding appropriate individual exposure assessment of metals and to provide valuable information on early diagnose of Mn exposure and toxicity. The use of new biomarker to understand the neurotoxic effects of exposure to Mn is critical to millions of workers who have been exposed to Mn for two main reasons. First, neurophysiological disorder is one of the main health issues for these workers; second, neurological impairment reduces the workers' productivity and is a major cause for work related injuries. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page